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Kazuhisa Yoshizawa,1 Masahiro Takeshima,2 Sayaka Ishino,3 Masaya Ogasawara,2 Dai Fujiwara,2 Yu Itoh,2 Aya Imanishi,2 Hidenobu Ohta,2 Kazuo Mishima2 1Department of Psychiatry, Akita Prefectural Center for Rehabilitation and Psychiatric Medicine, Daisen City, Akita, 019-2492, Japan; 2Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita City, Akita, 010-8543, Japan; 3Department of Neuropsychiatry, Sugawara Hospital, Yurihonjo City, Akita, 015-0012, JapanCorrespondence: Masahiro TakeshimaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita City, Akita, 010-8543, JapanTel +81-18-884-6122Fax +81-18-884-6445Email m.takeshima@med.akita-u.ac.jpPurpose: A major depressive episode is a risk factor for venous thromboembolism (VTE) in psychiatric inpatients. However, it is unclear whether the severity of depressive symptoms or duration of the current depressive episode is associated with VTE. Further, the VTE prevalence among hospitalized patients with a major depressive episode receiving electroconvulsive therapy is unknown. This retrospective study examined factors associated with VTE among hospitalized patients with a major depressive episode and estimated the prevalence of VTE in such patients who underwent electroconvulsive therapy.Patients and Methods: Patients with a major depressive episode hospitalized in the Department of Neuropsychiatry at Akita University Hospital between January 2018 and December 2020 were included. Data from the first week of hospitalization were extracted from medical records. VTE was diagnosed based on the findings of computed tomography. To evaluate whether the severity of depressive symptoms or duration of the current depressive episode was associated with VTE, logistic regression analysis was conducted after adjusting for covariates with known VTE risk factors (antidepressants, antipsychotics, and physical comorbidities).Results: We analyzed 133 patients; of these, 14 were diagnosed with asymptomatic VTE. The severity of depressive symptoms (odds ratio: 1.220, 95% confidence interval: 1.081– 1.377, p = 0.001) was significantly associated with VTE. The prevalence of VTE among those receiving electroconvulsive therapy was 35% (7/20).Conclusion: The prevalence of VTE was 35% among patients receiving in-hospital electroconvulsive therapy for a major depressive episode. VTE should be considered for hospitalized patients with severe depressive symptoms and patients receiving in-hospital electroconvulsive therapy for a major depressive episode.Keywords: bipolar depression, depressive symptoms, electroconvulsive therapy, unipolar depression, venous thromboembolism

Yu Tamada,1– 3 Takeshi Inoue,2 Atsushi Sekine,4 Hiroyuki Toda,5 Minoru Takeshima,2,6 Masaaki Sasaki,3 Keisuke Shindome,5 Wataru Morita,5 Nagisa Kuyama,3 Susumu Ohmae3 1Department of Psychiatry, Toranomon Hospital Kajigaya, Kawasaki, Kanagawa, Japan; 2Department of Psychiatry, Tokyo Medical University, Tokyo, Japan; 3Department of Psychiatry, Toranomon Hospital, Tokyo, Japan; 4The Medical Foundation of Keishin-Kai, Kei Mental Clinic, Daisen, Akita, Japan; 5Department of Psychiatry, National Defense Medical College, Tokorozawa, Saitama, Japan; 6Shibata Hospital, Takaoka, Toyama, JapanCorrespondence: Yu TamadaDepartment of Psychiatry, Toranomon Hospital Kajigaya, 1-3-1 Kajigaya, Takatsu-ku, Kawasaki, Kanagawa, 213-8587, JapanTel +81 44 877 5111Fax +81 44 877 5333Email y-tmd@umin.ac.jpPurpose: Melancholia has recently been re-evaluated, because patients with major depressive disorder (MDD) were found to be heterogeneous. However, the DSM-5 criteria for melancholia (DSM-MEL) have been criticized, because of the difficulty in clearly distinguishing between melancholic and non-melancholic depression using DSM-MEL. Psychomotor disturbance (PMD) is one of the most important, as well as one of the only measurable symptoms of melancholia. Parker et al developed the CORE measure, which assesses PMD as a behavioral characteristic. The aim of our study was to objectively identify the subjective symptoms of melancholia by analyzing the symptoms associated with PMD.Patients and Methods: A total of 106 participants with MDD were examined by psychiatrists. Multiple regression analysis was performed in which the total CORE score was the dependent variable, and items of the DSM-MEL and historically suggested melancholic features were independent variables.Results: The following five independent variables were able to predict the total CORE score: 1) feelings of having lost feeling, 2) depressive delusions, 3) perplexity, 4) indecisiveness, and 5) no aggression against others. These five variables were more strongly associated with the total CORE score than the DSM-MEL.Limitation: The major limitation of this study was that when choosing non-DSM melancholic signs and symptoms, we did not comprehensively evaluate and select the symptoms but chose items that are clinically important.Conclusion: We identified five subjective symptoms that were associated with PMD. These five symptoms may be clinically useful as diagnostic criteria for melancholia.Keywords: major depressive disorder, melancholic features, CORE measure, endogenous depression, diagnosis, psychomotor retardation

Masahiro Takeshima,1 Hiroyasu Ishikawa,1 Yoshiaki Umeta,2 Mizuki Kudoh,3 Akise Umakoshi,1 Kazuhisa Yoshizawa,4 Yu Ito,1 Tomoko Hosoya,1 Ko Tsutsui,1 Hidenobu Ohta,1 Kazuo Mishima1 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita 010-8543, Japan; 2Department of Psychiatry, Omagari City Hospital, Akita 014-0067, Japan; 3Department of Neuropsychiatry, Nakadori Rehabilitation Hospital, Akita 010-0001, Japan; 4Department of Psychiatry, Akita City Hospital, Akita 010-0933, JapanCorrespondence: Masahiro TakeshimaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita 010-8543, JapanTel +81-18-884-6122Fax +81-18-884-6445Email m.takeshima@med.akita-u.ac.jpPurpose: While depression has been recognized as a risk factor for venous thromboembolism (VTE), the prevalence of VTE in depressed inpatients has never been investigated. The aim of this study was thus to examine VTE prevalence and factors associated with VTE in depressed inpatients.Patients and Methods: We conducted a retrospective cross-sectional study of consecutive depressed inpatients (n = 94) from January 1, 2018, to June 30, 2019, at the psychiatry department of Akita University Hospital. As part of our clinical routine, depressed inpatients were screened for VTE using D-dimer, and patients who screened positive underwent enhanced CT to examine VTE. A variety of data was extracted from medical records, including, amongst others, age, sex, body mass index, diagnoses of psychiatric disorders, total scores on the 17-item Hamilton Depression Rating Scale, duration of current depressive episode, daily dosages of antidepressants and antipsychotics, catatonia, and physical restraint.Results: VTE was detected in 8.5% of depressed inpatients. There were no significant differences between VTE-positive and VTE-negative inpatients regarding any of the considered factors.Conclusion: Our analysis shows a VTE prevalence of 8.5% in depressed inpatients, higher than that of 2.3% reported in a previous study in hospitalized patients with psychiatric disorders including depression. This emphasizes the importance of VTE screening for depressive inpatients.Keywords: antidepressant, bipolar disorder, depression, sudden death, venous thrombosis

Masahiro Takeshima,1 Hiroyasu Ishikawa,2 Takashi Kanbayashi,1 Tetsuo Shimizu3 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita City, Akita 010-8543, Japan; 2Department of Neuropsychiatry, Nakadori Rehabilitation Hospital, Akita City, Akita 010-0001, Japan; 3Akita Prefectural Mental Health and Welfare Center, Akita City, Akita 010-0001, Japan Objective: Gabapentin and its prodrug are candidate therapeutic agents for akathisia. An open-label pilot study was conducted to investigate the therapeutic potential of gabapentin enacarbil (GE) for akathisia.Methods: In an open-labeled investigator-initiated clinical trial, nine outpatients with antipsychotics-induced akathisia were administered GE (300 or 600 mg/day) over 2 weeks. The BARS global akathisia score was used to assess akathisia. The BPRS was used to assess psychiatric symptoms. The subjects were also systematically questioned regarding the adverse events described in an interview form following GE treatment. An intension-to-treat analysis including all patients enrolled in the present study was completed.Results: One patient declined to participate further in the study on the third day after the start of treatment. Eight patients thus completed the entire trial (male: 2, female: 6, age [mean±SD]: 38.8±11.6 years). The average dosage of GE was 567 mg/day (300 mg/day [n=1], 600 mg/day [n=8]). The BARS global akathisia score significantly decreased after 1 and 2 weeks of treatment when compared to baseline (P=0.01 and P=0.01, respectively). There were no significant differences in BPRS score 1 or 2 weeks after the start of treatment. No serious adverse events occurred.Conclusion: GE has therapeutic potential for antipsychotics-induced akathisia. No additional risk of GE use for the management of akathisia was indicated. Keywords: clinical trial, antipsychotic agents, restless legs syndrome, schizophrenia

Yuki Omori,1 Takashi Kanbayashi,1,2 Yohei Sagawa,1 Aya Imanishi,1 Ko Tsutsui,1 Yuya Takahashi,1 Masahiro Takeshima,1 Manabu Takaki,3 Seiji Nishino,4 Tetsuo Shimizu1,2 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan; 2International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; 3Department of Neuropsychiatry, Okayama University Graduate School of Medicine, Okayama, Japan; 4Department of Psychiatry and Behavioral Sciences, Sleep and Circadian Neurobiology Laboratory & Center for Narcolepsy, Stanford University School of Medicine, Stanford, CA, USA Objectives: Delayed sleep phase syndrome (DSPS) is a chronic dysfunction of circadian rhythm of the subject that impairs functioning in social, occupational, or other spheres. High rate of depression is found among DSPS patients. Aripiprazole (APZ), a second-generation antipsychotic, is effective in treatment of depression as well as schizophrenia. Recently, few case reports show the effectiveness of APZ in treating DSPS and non-24-hour sleep–wake rhythm disorder. Therefore, we tried to treat DSPS with depression using APZ.Methods: Twelve subjects (including four women) aged 19–64 years were included. The subjects were prescribed initially 0.5–3 mg of APZ once a day with subsequent dose adjustments.Results: Sleep onset, midpoint of sleep, and sleep offset were significantly advanced by 1.1, 1.8, and 2.5 hours, respectively. Unexpectedly, sleep duration became significantly shorter by 1.3 hours after treatment. Their depressive moods showed an unremarkable change.Conclusion: Low dose of APZ advanced the sleep rhythm and reduced nocturnal sleep time in the subjects with DSPS. Since it is not easy for physicians to treat prolonged sleep duration often associated with DSPS, this medication would become a new therapeutic option for these patients. Keywords: delayed sleep phase syndrome, aripiprazole, total sleep time

Masahiro Takeshima,1,* Hiroyasu Ishikawa,1,2,* Kazumi Shimizu,3 Takashi Kanbayashi,1 Tetsuo Shimizu1 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan; 2Department of Neuropsychiatry, Nakadori Rehabilitation Hospital, Akita, Japan; 3Palliative Care Center, Akita University Hospital, Akita, Japan *These authors contributed equally to this work Purpose: Venous thromboembolism (VTE) is the combination of pulmonary embolism (PE) and deep vein thrombosis. In recent years, VTE has been gaining attention in the field of psychiatry as it can cause sudden deaths in patients hospitalized in psychiatric departments. The purpose of this study was to investigate the incidence of VTE in psychiatric inpatients using contrast-enhanced computed tomography (CT). Patients and methods: At the psychiatric department of the Akita University Hospital, NANOPIA® D-dimer was measured in patients with suspected symptomatic VTE or believed to be at risk for asymptomatic VTE. A follow-up contrast-enhanced CT was also performed in cases of D-dimer values over 1 µg/mL. Patients diagnosed with VTE based on contrast-enhanced CT during hospitalizations between May 1, 2009 and April 30, 2017 were analyzed. VTE incidence was compared in restrained and unrestrained catatonic and noncatatonic patients. We also investigated whether VTE was symptomatic or asymptomatic as well as its outcomes. Results: The overall incidence of VTE was 2.3% (39/1,681) in the 8-year period. VTE was observed in 61.1% (11/18) of catatonic patients, 4.1% (11/270) of noncatatonic restrained patients, and 1.2% (17/1,393) of noncatatonic unrestrained patients. PE was observed in 76.9% (30/39) of VTE patients and 97.4% (38/39) of VTE patients were asymptomatic. Recovery was achieved in all cases of VTE treated with anticoagulation therapy. Conclusion: These results indicate that the risk of VTE is high in psychiatric inpatients and that PE is common in these population. The data may also suggest that contrast-enhanced CT is important in surveying thrombus in suspected cases of VTE. In the psychiatric field, proper attention must be given to VTE, regardless of the presence or absence of catatonia or restraint, particularly given that PE was observed in more than 75% of cases of VTE. Keywords: computed tomography, deep vein thrombosis, D-dimer, psychiatric patients, catatonia, pulmonary embolism

Yuki Omori,1 Takashi Kanbayashi,1,2 Aya Imanishi,1 Ko Tsutsui,1 Yohei Sagawa,1 Yuka S Kikuchi,1 Masahiro Takeshima,1 Kazuhisa Yoshizawa,1 Sachiko Uemura,3 Tetsuo Shimizu1,2 1Department of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan; 2International Institute for Integrative Sleep Medicine (WPI-IIIS), University of Tsukuba, Tsukuba, Japan; 3Department of Physical Therapy, Akita University Graduate School of Health Sciences, Akita, Japan Purpose: Myotonic dystrophy type 1 (DM1) is often characterized by excessive daytime sleepiness (EDS) and sleep-onset rapid eye movement periods caused by muscleblind-like protein 2. The EDS tends to persist even after treatment of sleep apnea. We measured the cerebrospinal fluid (CSF) orexin levels in DM1 patients with EDS and compared the clinical characteristics with narcolepsy type 1 and idiopathic hypersomnia (IHS) patients.Patients and methods: We measured the CSF orexin levels in 17 DM1 patients with EDS and evaluated subjective sleepiness using the Epworth Sleepiness Scale (ESS), objective sleepiness using mean sleep latency (MSL), and sleep apnea using apnea-hypopnea index (AHI). We compared the ESS scores and MSL between decreased (≤200 pg/mL) and normal (>200 pg/mL) CSF orexin group in DM1 patients. Furthermore, we compared the CSF orexin levels, ESS scores, MSL, and AHI among patients with DM1, narcolepsy type 1 (n=46), and IHS (n=30).Results: Seven DM1 patients showed decreased CSF orexin levels. There were significant differences in the ESS scores and MSL between decreased and normal CSF orexin groups in DM1 patients. The ESS scores showed no significant difference among patients with DM1, narcolepsy type 1, and IHS. The MSL in DM1 and IHS patients were significantly higher than narcolepsy type 1 patients (p=0.01, p